1-Aryl-3,3-dimethyltriazenes: potential central nervous system active analogues of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC).

Abstract

A series of 19 aryldimethyltriazenes were synthesized as potential central nervous system (CNS) active analogues of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). The compounds were screened in mice against both intraperitoneally (ip) and intracerebrally (ic) implanted L1210 leukemia. Select compounds were further screened against ic implanted ependymoblastoma, and one compound was additionally screened against ic implanted B16 melanoma. Although several compounds were as effective as DTIC at prolonging the life span of mice bearing ip implanted L1210 leukemia, only 4-(3,3-dimethyl-1-triazeno)benzamide (DTB) and 4-(3,3-dimethyl-1-triazeno)benzoic acid (DTBA) were significantly active against the ic implanted tumor. DTB, unlike DTIC, was equally effective against both the ip and the ic implanted tumor, clearly indicating that it penetrated into the CNS in therapeutic concentration. DTB was also active against ic implanted ependymoblastoma and ic implanted B16 melanoma. Aryldimethyltriazenes, particularly DTB, may have a role in the treatment of tumors metastatic to the CNS. They may also be effective against primary brain tumors.

• Authors: D Farquhar, J Benvenuto
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 27 Issue 12 Pg. 1723-7 (Dec 1984) ISSN: 0022-2623 [Print] United States
• PMID: 6502603 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Dacarbazine

Topics

• Animals
• Antineoplastic Agents (chemical synthesis)
• Blood-Brain Barrier
• Brain Neoplasms (drug therapy)
• Dacarbazine (analogs & derivatives, chemical synthesis, toxicity)
• Drug Evaluation, Preclinical
• Ependymoma (drug therapy)
• Leukemia L1210 (drug therapy)
• Melanoma (drug therapy)
• Mice
• Mice, Inbred Strains
• Structure-Activity Relationship